A highly convergent and stereoselective total synthesis of the pentacyclic monocarboxylic acid ionophore monensin is presented. The proposed strategy involves formation of the monensin pentacyclic ring system as follows: CO yields ABCD yields ABCDE. The initial target for total synthesis is a tetracyclic polyether containing the monensin ABCD ring system. This tetracyclic key intermediate will be compared with material derived by degradation of the natural product. Key steps in the synthesis are: 1) the use of the permanganate oxidative cyclization of 1.5 dienes for for stereoselective synthesis of the CD rings; 2) the use of dimethylglutaric anhydride as a precursor of the monensin A ring, and E ring and side chain; and 3) the use of a directed aldol condensation for coupling of an A-ring and CD fragment, and elaboration of the B-ring via a highly branched 3-deoxy-2-ketofuranose intermediate. Monensin is a member of the class of Streptomyces mold metabolites known as monocarboxylic acid ionophores. Members of this class of natural products possess interesting biological properties, including commercially important coccidiostatt activity in poultry and parmaceutically interesting cardiotonic properties (strong positive inotropic effect, increased cardiac output, and increased coronary flow). We hope that methodology developed in this work will make available new ionophores with improved beneficial properties.